ArticleThe Journal of clinical endocrinology and metabolism2017
Galactose Supplementation in Patients With TMEM165-CDG Rescues the Glycosylation Defects.
Article in The Journal of clinical endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 80 citations in OpenAlex.
- D-galactose supplementation in individuals with PMM2-CDG: results of a multicenter, open label, prospective pilot clinical trial.Orphanet journal of rare diseases · 2021Trial
- Endocrine Implications of Congenital Disorders of GlycosylationJournal of clinical research in pediatric endocrinology · 2026Review
- Galactose treatment rescues neuromuscular junction transmission in glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) deficient mice.Human molecular genetics · 2025Article
- Glycosphingolipid synthesis is impaired in SLC35A2-CDG and improves with galactose supplementation.Cellular and molecular life sciences : CMLS · 2025Article
- Lysosomal TMEM165 controls cellular ion homeostasis and survival by mediating lysosomal CaNature communications · 2025Article
- Putative role of TMEM165 in congenital cardiomyopathies.Frontiers in molecular neuroscience · 2025Review
- Inherited metabolic epilepsies-established diseases, new approaches.Epilepsia open · 2024Review
- Unique Glycans in Synaptic Glycoproteins in Mouse Brain.ACS chemical neuroscience · 2024Article
- Article
- Combination of the CRAC Channel Inhibitor CM4620 and Galactose as a Potential Therapy for Acute Pancreatitis.Function (Oxford, England) · 2024Article
- Liposome-encapsulated mannose-1-phosphate therapy improves global N-glycosylation in different congenital disorders of glycosylation.Molecular genetics and metabolism · 2024Article
- Insights into the regulation of cellular MnBiochimica et biophysica acta. Molecular basis of disease · 2023Article
- Syntaxin-5's flexibility in SNARE pairing supports Golgi functions.Traffic (Copenhagen, Denmark) · 2023Article
- The role of CaCell calcium · 2023Review
- Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease.International journal of molecular sciences · 2023Article
- New insights into the pathogenicity of TMEM165 variants using structural modeling based on AlphaFold 2 predictions.Computational and structural biotechnology journal · 2023Article
- Identification of a Novel Prognostic Signature Based on N-Linked Glycosylation and Its Correlation with Immunotherapy Response in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Article
- Chemical Therapies for Congenital Disorders of Glycosylation.ACS chemical biology · 2022Review
- CAMLG-CDG: a novel congenital disorder of glycosylation linked to defective membrane trafficking.Human molecular genetics · 2022Article
- Nutrition interventions in congenital disorders of glycosylation.Trends in molecular medicine · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
contextTMEM165 deficiency is a severe multisystem disease that manifests with metabolic, endocrine, and skeletal involvement. It leads to one type of congenital disorders of glycosylation (CDG), a rapidly growing group of inherited diseases in which the glycosylation process is altered. Patients have decreased galactosylation by serum glycan analysis. There are >100 CDGs, but only specific types are treatable.
objectiveGalactose has been shown to be beneficial in other CDG types with abnormal galactosylation. The aim of this study was to characterize the effects of galactose supplementation on Golgi glycosylation in TMEM165-depleted HEK293 cells, as well as in 2 patients with TMEM165-CDG and in their cultured skin fibroblast cells. DESIGN AND
settingGlycosylation was assessed by mass spectrometry, western blot analysis, and transferrin isoelectrofocusing. PATIENTS AND
interventionsBoth unrelated patients with TMEM165-CDG with the same deep intronic homozygous mutation (c.792+182G>A) were allocated to receive d-galactose in a daily dose of 1 g/kg.
resultsWe analyzed N-linked glycans and glycolipids in knockout TMEM165 HEK293 cells, revealing severe hypogalactosylation and GalNAc transfer defects. Although these defects were completely corrected by the addition of Mn2+, we demonstrated that the observed N-glycosylation defect could also be overcome by galactose supplementation. We then demonstrated that oral galactose supplementation in patients with TMEM165-deficient CDG improved biochemical and clinical parameters, including a substantial increase in the negatively charged transferrin isoforms, and a decrease in hypogalactosylated total N-glycan structures, endocrine function, and coagulation parameters.
conclusionTo our knowledge, this is the first description of abnormal glycosylation of lipids in the TMEM165 defect and the first report of successful dietary treatment in TMEM165 deficiency. We recommend the use of oral d-galactose therapy in TMEM165-CDG.
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